Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model

• DOI: 10.1038/s41467-018-07008-0
• Publication Date: 2018-10-26T10:04:36Z
• Authors: Mark J. Bailey; James Duehr; Harrison Dulin; Felix Broecker; Julia A. Brown; Fortuna O. Arumemi; Maria C. Bermúdez...; Victor H. Leyva-G...; Matthew J. Evans; Viviana Simon; Jean K. Lim; Florian Krammer; Rong Hai; Peter Palese; Gene S. Tan
• Keywords: Zika Virus; Flavivirus; Antibody-dependent enhancement; Vero cell

Abstract Zika virus is a mosquito-borne flavivirus closely related to dengue that can cause severe disease in humans, including microcephaly newborns and Guillain-Barré syndrome adults. Specific treatments vaccines for are not currently available. Here, we isolate characterize four monoclonal antibodies (mAbs) from an infected patient target the non-structural protein NS1. We show while these non-neutralizing, NS1-specific mAbs engage FcγR without inducing antibody dependent enhancement (ADE) of infection vitro. Moreover, demonstrate mAb AA12 has protective efficacy against lethal challenges African Asian lineage strains Stat2 –/– mice. Protection Fc-dependent, as mutated unable activate known Fc effector functions or complement vivo. This study highlights importance ZIKV NS1 potential vaccine antigen.